Heat shock proteins (HSPs) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, we have examined the expression of hsf and HSP genes in normal human prostate epithelial cells and a range of prostate carcinoma cell lines derived from human tumors. We have observed elevated expressions of HSF1, HSP60, and HSP70 in the aggressively malignant cell lines PC-3, DU-145, and CA-HPV-10. Elevated HSP expression in cancer cell lines appeared to be regulated at the post–messenger ribonucleic acid (mRNA) levels, as indicated by gene chip microarray studies, which indicated little difference in heat shock factor (HSF) or HSP mRNA expression between the normal and malignant prostate cell lines. When we compared the expression patterns of constitutive HSP genes between PC-3 prostate carcinoma cells growing as monolayers in vitro and as tumor xenografts growing in nude mice in vivo, we found a marked reduction in expression of a wide spectrum of the HSPs in PC-3 tumors. This decreased HSP expression pattern in tumors may underlie the increased sensitivity to heat shock of PC-3 tumors. However, the induction by heat shock of HSP genes was not markedly altered by growth in the tumor microenvironment, and HSP40, HSP70, and HSP110 were expressed abundantly after stress in each growth condition. Our experiments indicate therefore that HSF and HSP levels are elevated in the more highly malignant prostate carcinoma cells and also show the dominant nature of the heat shock–induced gene expression, leading to abundant HSP induction in vitro or in vivo.
Heat shock transcription factor 1 (HSF1) monitors the structural integrity of intracellular proteins and its regulation is essential for the health and longevity of eukaryotic organisms. HSF1 also plays a role in the acute inflammatory response in the negative regulation of cytokine gene transcription. Here we show, for the first time, that HSF1 is regulated by the proinflammatory protein kinase MAPKAP kinase 2 (MK2). We have shown that MK2 directly phosphorylates HSF1 and inhibits activity by decreasing its ability to bind the heat shock elements (HSE) found in the promoters of target genes encoding the HSP molecular chaperones and cytokine genes. We show that activation of HSF1 to bind HSE in hsp promoters is inhibited through the phosphorylation of a specific residue, serine 121 by MK2. A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1. Dephosphorylation of serine 121 in cells exposed to non-steroidal anti-inflammatory drugs leads to HSP90 dissociation from HSF1, which then forms active DNA binding trimers. These experiments indicate a novel mechanism for the regulation of HSF1 by proinflammatory signaling and may permit HSF1 to respond rapidly to extracellular events, permitting optimal physiological regulation.
Plant associated bacteria are promising alternatives to chemical fertilizers for plant growth and yield improvement in an eco-friendly manner. In this study, rice associated bacteria were isolated and assessed for mineral phosphate solubilization and indole-3-acetic acid (IAA) production activity in vitro. Six promising strains, which were tentatively identified as phylotaxon Pseudochrobactrum sp. (BRRh-1), Burkholderia sp. (BRRh-2), Burkholderia sp. (BRRh-3), Burkholderia sp. (BRRh-4), Pseudomonas aeruginosa (BRRh-5 and BRRh-6) based on their 16S rRNA gene phylogeny, exhibited significant phosphate solubilizing activity in National Botanical Research Institute phosphate growth medium, and BRRh-4 displayed the highest phosphate solubilizing activity, followed by BRRh-5. The pH of the culture broth declined, resulting in increase of growth rate of bacteria at pH 7, which might be due to organic acid secretion by the strains. In presence of L-tryptophan, five isolates synthesized IAA and the maximum IAA was produced by BRRh-2, followed by BRRh-1. Application of two most efficient phosphate solubilizing isolates BRRh-4 and BRRh-5 by root dipping (colonization) of seedling and spraying at the flowering stage significantly enhanced the growth and grain yield of rice variety BRRI dhan-29. Interestingly, application of both strains with 50% of recommended nitrogen, phosphorus and potassium fertilizers produced equivalent or higher grain yield of rice compared to the control grown with full recommended fertilizer doses, which suggests that these strains may have the potential to be used as bioinoculants for sustainable rice production